Oxidative Pentose Phosphate Pathway Enzyme 6-Phosphogluconate Dehydrogenase Plays a Key Role in Breast Cancer Metabolism.
6PGD
breast cancer
cancer metabolism
pentose phosphate pathway
Journal
Biology
ISSN: 2079-7737
Titre abrégé: Biology (Basel)
Pays: Switzerland
ID NLM: 101587988
Informations de publication
Date de publication:
23 Jan 2021
23 Jan 2021
Historique:
received:
31
12
2020
revised:
18
01
2021
accepted:
20
01
2021
entrez:
27
1
2021
pubmed:
28
1
2021
medline:
28
1
2021
Statut:
epublish
Résumé
The pentose phosphate pathway (PPP) plays an essential role in the metabolism of breast cancer cells for the management of oxidative stress and the synthesis of nucleotides. 6-phosphogluconate dehydrogenase (6PGD) is one of the key enzymes of the oxidative branch of PPP and is involved in nucleotide biosynthesis and redox maintenance status. Here, we aimed to analyze the functional importance of 6PGD in a breast cancer cell model. Inhibition of 6PGD in MCF7 reduced cell proliferation and showed a significant decrease in glucose consumption and an increase in glutamine consumption, resulting in an important alteration in the metabolism of these cells. No difference in reactive oxygen species (ROS) production levels was observed after 6PGD inhibition, indicating that 6PGD, in contrast to glucose 6-phosphate dehydrogenase, is not involved in redox balance. We found that 6PGD inhibition also altered the stem cell characteristics and mammosphere formation capabilities of MCF7 cells, opening new avenues to prevent cancer recurrance after surgery or chemotherapy. Moreover, inhibition of 6PGD via chemical inhibitor S3 resulted in an induction of senescence, which, together with the cell cycle arrest and apoptosis induction, might be orchestrated by p53 activation. Therefore, we postulate 6PGD as a novel therapeutic target to treat breast cancer.
Identifiants
pubmed: 33498665
pii: biology10020085
doi: 10.3390/biology10020085
pmc: PMC7911610
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministerio de Economía, Industria y Competitividad, Gobierno de España
ID : SAF2017-89673-R
Organisme : Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
ID : CB17/04/00023
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2017SGR1033
Organisme : Institució Catalana de Recerca i Estudis Avançats
ID : Icrea Academia award granted to M Cascante
Références
Cell Death Differ. 2014 Sep;21(9):1451-9
pubmed: 24874608
Metab Eng. 2013 Jan;15:34-47
pubmed: 23111062
Oncotarget. 2016 Jan 19;7(3):2910-20
pubmed: 26543237
J Cell Sci. 1993 Jul;105 ( Pt 3):607-12
pubmed: 8408290
Cancers (Basel). 2019 Aug 01;11(8):
pubmed: 31374935
Am J Med Sci. 2020 Sep;360(3):279-286
pubmed: 32829780
Oncotarget. 2017 Oct 7;8(63):106693-106706
pubmed: 29290982
Cancer Lett. 2011 Jan 1;300(1):20-9
pubmed: 20884117
Exp Cell Res. 1999 Aug 25;251(1):16-21
pubmed: 10438567
Nat Rev Drug Discov. 2011 Aug 31;10(9):671-84
pubmed: 21878982
Free Radic Biol Med. 2012 Aug 1;53(3):421-36
pubmed: 22580150
Cancer Lett. 2015 Jan 28;356(2 Pt A):197-203
pubmed: 24374014
Int J Mol Sci. 2020 Jan 31;21(3):
pubmed: 32023830
Trends Biochem Sci. 2014 Aug;39(8):347-54
pubmed: 25037503
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Int J Mol Sci. 2020 May 12;21(10):
pubmed: 32408513
Clin Transl Oncol. 2018 Sep;20(9):1145-1152
pubmed: 29340974
Mol Cell. 2019 Dec 19;76(6):857-871.e9
pubmed: 31586547
Int J Cancer. 2009 Jun 15;124(12):2789-96
pubmed: 19253370
J Biol Chem. 1982 Aug 25;257(16):9424-8
pubmed: 6213607
IUBMB Life. 2012 May;64(5):362-9
pubmed: 22431005
Mol Metab. 2020 Mar;33:2-22
pubmed: 31685430
Oncol Lett. 2019 May;17(5):4213-4221
pubmed: 30944616
Mol Cell. 2014 Aug 21;55(4):552-65
pubmed: 25042803
Nat Rev Drug Discov. 2009 Jul;8(7):579-91
pubmed: 19478820
J Cancer. 2017 Sep 12;8(16):3131-3141
pubmed: 29158785
Cancer Res. 2012 Nov 15;72(22):5712-20
pubmed: 22986741
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
pubmed: 6606682
Clin Transl Oncol. 2019 Apr;21(4):404-411
pubmed: 30182212
Nat Rev Drug Discov. 2013 Nov;12(11):829-46
pubmed: 24113830
Br J Cancer. 1992 Jul;66(1):185-91
pubmed: 1637668
Biochem Biophys Res Commun. 2013 Sep 20;439(2):247-51
pubmed: 23973484
Cell Death Dis. 2015 Mar 05;6:e1675
pubmed: 25741600
Nat Commun. 2011 Sep 13;2:473
pubmed: 21915115
J Clin Invest. 2013 Sep;123(9):3678-84
pubmed: 23999442
EMBO J. 1995 Nov 1;14(21):5209-15
pubmed: 7489710
Trends Biochem Sci. 2010 Aug;35(8):427-33
pubmed: 20570523
Nat Cell Biol. 2011 Mar;13(3):310-6
pubmed: 21336310
Pharmacol Ther. 2013 May;138(2):255-71
pubmed: 23356980
Trends Cancer. 2015 Nov 1;1(3):161-173
pubmed: 26870836
Biochem J. 2003 Mar 15;370(Pt 3):935-43
pubmed: 12466018
Biomed Pharmacother. 2019 Mar;111:1353-1358
pubmed: 30841449
Front Endocrinol (Lausanne). 2020 Jun 09;11:365
pubmed: 32582032
J Biol Chem. 1979 Nov 10;254(21):10644-8
pubmed: 500601
Neoplasia. 2000 Jul-Aug;2(4):291-9
pubmed: 11005563
Mol Genet Metab. 2010 Aug;100(4):372-8
pubmed: 20483646
Int J Biochem Cell Biol. 2016 Mar;72:18-26
pubmed: 26772821
Free Radic Biol Med. 2010 Aug 1;49(3):361-73
pubmed: 20420899
Cancer Manag Res. 2020 Aug 05;12:6921-6934
pubmed: 32801914
EMBO Rep. 2014 Nov;15(11):1139-53
pubmed: 25312810
Biofactors. 2020 Jul;46(4):550-562
pubmed: 32039535
Metabolomics. 2012 Jun 1;8(3):454-464
pubmed: 22661920
PLoS Biol. 2019 Aug 28;17(8):e3000425
pubmed: 31461438
FEBS Lett. 2012 Jul 30;586(16):2389-95
pubmed: 22677172
PLoS Genet. 2011 Aug;7(8):e1002229
pubmed: 21852960
Nat Cell Biol. 2015 Nov;17(11):1484-96
pubmed: 26479318
Oncogene. 2016 Jul 7;35(27):3544-54
pubmed: 26568303
J Immunol. 1992 Jan 15;148(2):514-23
pubmed: 1309560
Int J Radiat Biol. 2019 Jul;95(7):912-919
pubmed: 30822194
Int J Cancer. 2006 Dec 15;119(12):2733-41
pubmed: 17019714
Biomolecules. 2020 Mar 08;10(3):
pubmed: 32182711
Science. 1956 Feb 24;123(3191):309-14
pubmed: 13298683
Cancer Biomark. 2007;3(4-5):245-50
pubmed: 17917153